Human Papillomavirus Vaccine Immunogenicity and Safety Trial in Young Adult Women With GSK Biologicals Novel HPV Vaccine

A Long-term, Follow-up of the Immunogenicity and Safety of GlaxoSmithKline Biologicals' Novel HPV Vaccine in Healthy Female Subjects Vaccinated in the Primary Study

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Indeed, certain oncogenic types of HPV can infect the cervix (part of the uterus or womb). This infection may go away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. GlaxoSmithKline Biological's has developed a HPV vaccine against the oncogenic types HPV-16 and HPV-18 formulated with the AS04 adjuvant (control vaccine) and is also evaluating novel HPV vaccines formulations. This study will evaluate the long-term immunogenicity and safety of a novel GSK Biological's vaccine in approximately 376 subjects who received the novel vaccine or the control vaccine administered in the primary study.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus; Papillomavirus Vaccines
• Intervention / Treatment: Biological: CervarixTM; Biological: HPV investigational vaccine GSK568893A, different formulations

• Study Type: Interventional
• Enrollment (Actual): 383
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • GSK Investigational Site
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
  • Liège, Belgium, 4000
    • GSK Investigational Site
  • Tienen, Belgium, 3300
    • GSK Investigational Site
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site
• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • GSK Investigational Site
    • Golden, Colorado, United States, 80401
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • GSK Investigational Site
    • Salt Lake City, Utah, United States, 84121
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• A female who enrolled in the study 102115 and received three doses of vaccine.
• Written informed consent obtained from the subject prior to enrolment.

Exclusion Criteria:

• Use (or planned use during the study period) of any investigational or non-registered product or off-label use of licensed product (drug or vaccine).
• Chronic administration of immunosuppressants or other immune-modifying drugs occurring less than three months prior to blood sampling.
• Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.
• Planned administration of any HPV vaccine, other than that foreseen by the study protocol, during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cervarix Group; Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: CervarixTM; Subjects were administered three doses of HPV vaccine
Experimental: Cervarix 1 Group; Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 1 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: HPV investigational vaccine GSK568893A, different formulations; Subjects were administered three doses of HPV investigational vaccine
Experimental: Cervarix 2 Group; Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 2 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: HPV investigational vaccine GSK568893A, different formulations; Subjects were administered three doses of HPV investigational vaccine
Experimental: Cervarix 3 Group; Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 3 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: HPV investigational vaccine GSK568893A, different formulations; Subjects were administered three doses of HPV investigational vaccine
Experimental: Cervarix 4 Group; Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 4 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: HPV investigational vaccine GSK568893A, different formulations; Subjects were administered three doses of HPV investigational vaccine
Experimental: Cervarix 5 Group; Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 5 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: HPV investigational vaccine GSK568893A, different formulations; Subjects were administered three doses of HPV investigational vaccine
Experimental: Cervarix 6 Group; Female subjects, aged 18 to 25 years at the time of first vaccination, received 3 doses of Cervarix vaccine formulation 6 at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid region of the non-dominant arm.	Biological: HPV investigational vaccine GSK568893A, different formulations; Subjects were administered three doses of HPV investigational vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) Antibodies.	Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 8 ELISA units per milliliter (EL.U/mL).	At Months 18, 24, 36 and 48.
Geometric Mean Titers (GMTs) for Human Papillomavirus-16 (HPV-16) Antibodies.	Antibody titers were expressed as GMTs. The reference cut-off value was greater than or equal to (≥) 8 EL.U/mL.	At Months 18, 24, 36 and 48.
Geometric Mean Titers (GMTs) for Human Papillomavirus-16 (HPV-16) Antibodies	Antibody titers were expressed as GMTs. The reference cut-off value was greater than or equal to (≥) 8 EL.U/mL.	At Months 18, 24, 36 and 48.
Number of Seroconverted Subjects Against Human Papillomavirus-18 (HPV-18) Antibodies.	Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 7 EL.U/mL.	At Months 18, 24, 36 and 48.
Geometric Mean Titers (GMTs) for Human Papillomavirus-18 (HPV-18) Antibodies.	Antibody titers were expressed as GMTs. The reference cut-off value was ≥ 7 EL.U/mL.	At Months 18, 24, 36 and 48.
Geometric Mean Titers (GMTs) for Human Papillomavirus-18 (HPV-18) Antibodies	Antibody titers were expressed as GMTs. The reference cut-off value was greater than or equal to (≥) 7 EL.U/mL.	At Months 18, 24, 36 and 48.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroconverted Subjects Against Human Papillomavirus-31 (HPV-31) Antibodies.	Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 59 EL.U/mL.	At Months 18, 24, 36 and 48.
Geometric Mean Titers (GMTs) for Human Papillomavirus-31 (HPV-31) Antibodies.	Antibody titers were expressed as GMTs. The reference cut-off value was ≥ 59 EL.U/mL.	At Months 18, 24, 36 and 48.
Number of Seroconverted Subjects Against Human Papillomavirus-45 (HPV-45) Antibodies.	Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. Seronegative subjects are subjects who had an antibody concentration below cut-off value. The assessed cut-off value was 59 EL.U/mL.	At Months 18, 24, 36 and 48.
Geometric Mean Titers (GMTs) for Human Papillomavirus-45 (HPV-45) Antibodies.	Antibody titers were expressed as GMTs. The reference cut-off value was ≥ 59 EL.U/mL.	At Months 18, 24, 36 and 48.
Number of Subjects With at Least One New Onset of Chronic Disease (NOCDs)	NOCDs include conditions such as diabetes, autoimmune disease, asthma, allergies etc. At least one NOCD = At least one NOCD experienced (regardless of the Medical Dictionary for Regulatory Activities [MedDRA] Preferred Term)	From Month 0 to Months 18, 24, 36 and 48
Number of Subjects With at Least One Medically Significant Condition (MAEs).	MAEs were defined as adverse events (AEs) prompting emergency room or physician visits that were not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities, and injury. At least one MAE = At least one medically significant AE experienced (regardless of the MedDRA Preferred Term).	From Month 0 to Months 18, 24, 36 and 48
Number of Subjects With Any Serious Adverse Events (SAEs).	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity, or are a congenital anomaly/birth defect in the offspring of a study subject. Any = Occurrence of any symptom regardless of intensity grade.	From Month 0 to Months 18, 24, 36 and 48
Number of Subjects With Pregnancy Outcomes.	Pregnancy outcomes were healthy baby, spontaneous abortion and elective abortion.	From Month 0 to Month 18
Number of Subjects With Pregnancy Outcomes.	Pregnancy outcomes were healthy baby, spontaneous abortion, elective abortion and ongoing pregnancy.	From Month 0 to Month 24
Number of Subjects With Pregnancy Outcomes.	Pregnancy outcomes were healthy baby, abnormal infant/congenital anomaly, spontaneous abortion and elective abortion.	From Month 0 to Month 36
Number of Subjects With Pregnancy Outcomes.	Pregnancy outcomes were normal infant, abnormal infant/congenital anomaly, spontaneous abortion and elective termination.	From Month 0 to Month 48

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2006
• Primary Completion (Actual): January 30, 2007
• Study Completion (Actual): January 30, 2007

Study Registration Dates

• First Submitted: July 18, 2006
• First Submitted That Met QC Criteria: August 1, 2006
• First Posted (Estimate): August 2, 2006

Study Record Updates

• Last Update Posted (Actual): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 27, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: HPV vaccine
• Other Study ID Numbers: 108052 (FU month 18); 2004-003766-14 (EudraCT Number); 107919 (Other Identifier: GSK); 107921 (Other Identifier: GSK); 107918 (Other Identifier: GSK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 108052 (FU month 18)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 108052 (FU month 18)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 108052 (FU month 18)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 108052 (FU month 18)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 108052 (FU month 18)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register